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The Lancet. Diabetes & Endocrinology Dec 2021Primary aldosteronism is a common cause of secondary hypertension associated with excess cardiovascular morbidities. Primary aldosteronism is underdiagnosed because it... (Review)
Review
Primary aldosteronism is a common cause of secondary hypertension associated with excess cardiovascular morbidities. Primary aldosteronism is underdiagnosed because it does not have a specific, easily identifiable feature and clinicians can be poorly aware of the disease. The diagnostic investigation is a multistep process of screening, confirmatory testing, and subtype differentiation of unilateral from bilateral forms for therapeutic management. Adrenal venous sampling is key for reliable subtype identification, but can be bypassed in patients with specific characteristics. For unilateral disease, surgery offers the possibility of cure, with total laparoscopic unilateral adrenalectomy being the treatment of choice. Bilateral forms are treated mainly with mineralocorticoid receptor antagonists. The goals of treatment are to normalise both blood pressure and excessive aldosterone production, and the primary aims are to reduce associated comorbidities, improve quality of life, and reduce mortality. Prompt diagnosis of primary aldosteronism and the use of targeted treatment strategies mitigate aldosterone-specific target organ damage and with appropriate patient management outcomes can be excellent. Advances in molecular histopathology challenge the traditional concept of primary aldosteronism as a binary disease, caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations drive autonomous aldosterone production in most adenomas. Many of these same mutations have been identified in nodular lesions adjacent to an aldosterone-producing adenoma and in patients with bilateral disease. In addition, germline mutations cause rare familial forms of aldosteronism (familial hyperaldosteronism types 1-4). Genetic testing for inherited forms in suspected cases of familial hyperaldosteronism avoids the burdensome diagnostic investigation in positive patients. In this Review, we discuss advances and future management approaches in the diagnosis of primary aldosteronism.
Topics: Adenoma; Adrenalectomy; Adrenocortical Adenoma; Aldosterone; Humans; Hyperaldosteronism; Hypertension; Quality of Life
PubMed: 34798068
DOI: 10.1016/S2213-8587(21)00210-2 -
The Veterinary Clinics of North... Sep 2020Primary hyperaldosteronism, also known as Conn's syndrome, is the most common adrenocortical disease in cats. As in humans, this disease is underdiagnosed in cats. Cats... (Review)
Review
Primary hyperaldosteronism, also known as Conn's syndrome, is the most common adrenocortical disease in cats. As in humans, this disease is underdiagnosed in cats. Cats presenting with systemic arterial hypertension, hypokalemia, or both quite often are only treated symptomatically without further investigations. This practice may potentially exclude a significant number of cats from receiving appropriate treatment. It is therefore important for general practitioners to be aware of the disease. This article describes the (patho)physiology, clinical presentation, diagnostic approach, and treatment options of for feline primary hyperaldosteronism.
Topics: Animals; Cat Diseases; Cats; Hyperaldosteronism
PubMed: 32653266
DOI: 10.1016/j.cvsm.2020.05.007 -
Nature Reviews. Endocrinology Oct 2020Early diagnosis and appropriate treatment of primary aldosteronism, the most frequent cause of secondary hypertension, are crucial to prevent deleterious cardiovascular... (Review)
Review
Early diagnosis and appropriate treatment of primary aldosteronism, the most frequent cause of secondary hypertension, are crucial to prevent deleterious cardiovascular outcomes. In the past decade, the discovery of genetic abnormalities responsible for sporadic and familial forms of primary aldosteronism has improved the knowledge of the pathogenesis of this disorder. Mutations in genes encoding ion channels and pumps lead to increased cytosolic concentrations of calcium in zona glomerulosa cells, which triggers CYP11B2 expression and autonomous aldosterone production. Improved understanding of the mechanisms underlying the disease is key to improving diagnostics and to developing and implementing targeted treatments. This Review provides an update on the genetic abnormalities associated with sporadic and familial forms of primary aldosteronism, their frequency among different populations and the mechanisms explaining excessive aldosterone production and adrenal nodule development. The possible effects and uses of these findings for improving the diagnostics for primary aldosteronism are discussed. Furthermore, current treatment options of primary aldosteronism are reviewed, with particular attention to the latest studies on blood pressure and cardiovascular outcomes following medical or surgical treatment. The new perspectives regarding the use of targeted drug therapy for aldosterone-producing adenomas with specific somatic mutations are also addressed.
Topics: Adrenal Glands; Aldosterone; Animals; Humans; Hyperaldosteronism; Hypertension; Mutation
PubMed: 32724183
DOI: 10.1038/s41574-020-0382-4 -
The Journal of Clinical Endocrinology... Dec 2020New approaches are needed to address the evolution of the primary aldosteronism syndrome and to increase its recognition. Herein, we review evidence indicating that... (Review)
Review
CONTEXT
New approaches are needed to address the evolution of the primary aldosteronism syndrome and to increase its recognition. Herein, we review evidence indicating that primary aldosteronism is a prevalent syndrome that is mostly unrecognized, and present a pragmatic and pathophysiology-based approach to improve diagnosis and treatment.
METHODS
Evidence was gathered from published guidelines and studies identified from PubMed by searching for primary aldosteronism, aldosterone, renin, and hypertension. This evidence was supplemented by the authors' personal knowledge, research experience, and clinical encounters in primary aldosteronism.
INTERPRETATION OF EVIDENCE
Renin-independent aldosterone production is a prevalent phenotype that is diagnosed as primary aldosteronism when severe in magnitude, but is largely unrecognized when milder in severity. Renin-independent aldosterone production can be detected in normotensive and hypertensive individuals, and the magnitude of this biochemical phenotype parallels the magnitude of blood pressure elevation, the risk for incident hypertension and cardiovascular disease, and the likelihood and magnitude of blood pressure reduction with mineralocorticoid receptor antagonist therapy. Expansion of the indications to screen for primary aldosteronism, combined with the use of a pathophysiology-based approach that emphasizes inappropriate aldosterone production in the context of renin suppression, will substantially increase the diagnostic and therapeutic yields for primary aldosteronism.
CONCLUSIONS
The landscape of primary aldosteronism has evolved to recognize that it is a prevalent syndrome of renin-independent aldosterone production that contributes to the pathogenesis of hypertension and cardiovascular disease. Expanding screening indications and simplifying the diagnostic approach will enable implementation of targeted treatment for primary aldosteronism.
Topics: Aldosterone; Blood Pressure; Diagnostic Techniques, Endocrine; Humans; Hyperaldosteronism; Hypertension; Mass Screening; Practice Guidelines as Topic; Prevalence; Prognosis; Renin; Syndrome
PubMed: 32865201
DOI: 10.1210/clinem/dgaa606 -
Journal of the American College of... Dec 2019Primary aldosteronism (PA) is a common, but frequently overlooked, cause of arterial hypertension and excess cardiovascular events, particularly atrial fibrillation. As... (Review)
Review
Primary aldosteronism (PA) is a common, but frequently overlooked, cause of arterial hypertension and excess cardiovascular events, particularly atrial fibrillation. As timely diagnosis and treatment can provide a cure of hyperaldosteronism and hypertension, even when the latter is resistant to drug treatment, strategies to screen patients for PA early with a simplified diagnostic algorithm are justified. They can be particularly beneficial in some subgroups of hypertensive patients, as those who are at highest cardiovascular risk. However, identification of the surgically curable cases of PA and achievement of optimal results require subtyping with adrenal vein sampling, which, as it is technically challenging and currently performed only in tertiary referral centers, represents the bottleneck in the work-up of PA. Measures aimed at improving the clinical use of adrenal vein sampling and at developing alternative techniques for subtyping, alongside recommendations for drug treatment, including new development in the field, and for follow-up are discussed.
Topics: Adrenal Glands; Aldosterone; Diagnosis, Differential; Humans; Hyperaldosteronism; Hypertension
PubMed: 31779795
DOI: 10.1016/j.jacc.2019.09.057 -
Reviews in Endocrine & Metabolic... Feb 2023Primary aldosteronism (PA) is the most common form of secondary hypertension. Although hypertensive disorders seem to affect around 5-10% of pregnancies worldwide,... (Review)
Review
Primary aldosteronism (PA) is the most common form of secondary hypertension. Although hypertensive disorders seem to affect around 5-10% of pregnancies worldwide, literature counts less than 80 cases of PA diagnosed during the peri-partum period. In this review we discuss about current knowledge on pathophysiology, natural history, diagnosis and treatment of PA in pregnancy. Because of the physiologic changes in the renin-angiotensin-aldosterone system (RAAS) and the contraindication to both confirmatory test and subtype differentiation, diagnosis of PA during pregnancy is challenging and relies mostly on detection of low/suppressed renin and high aldosterone levels. The course of pregnancy in patients with PA is highly variable, ranging from progesterone-induced amelioration of blood pressure (BP) control to severe and resistant hypertension with potential maternal and fetal complications. Mineralcorticoid receptor antagonists (MRA) are the recommended and most effective drugs for treatment of PA. As the anti-androgenic effect of spironolactone can potentially interfere with sexual development, their prescription is not recommended during pregnancy. On the other side, eplerenone, has proven to be safe and effective in 6 pregnant women and may be added to conventional first line drug regimen in presence of resistant hypertension or persistent hypokalemia. Ideally, patients with unilateral forms of PA should undergo adrenalectomy prior to conception, however, when PA is diagnosed during pregnancy and medical therapy fails to adequately control hypertension or its complications, adrenalectomy can be considered during the second trimester in case of unilateral adrenal mass at MRI-scan.
Topics: Humans; Female; Pregnancy; Hyperaldosteronism; Mineralocorticoid Receptor Antagonists; Spironolactone; Hypertension; Eplerenone
PubMed: 35536535
DOI: 10.1007/s11154-022-09729-6 -
Circulation Aug 2018Primary aldosteronism (PA) is the most common form of secondary hypertension. In many cases, somatic mutations in ion channels and pumps within adrenal cells initiate... (Review)
Review
Primary aldosteronism (PA) is the most common form of secondary hypertension. In many cases, somatic mutations in ion channels and pumps within adrenal cells initiate the pathogenesis of PA, and this mechanism might explain why PA is so common and suggests that milder and evolving forms of PA must exist. Compared with primary hypertension, PA causes more end-organ damage and is associated with excess cardiovascular morbidity, including heart failure, stroke, nonfatal myocardial infarction, and atrial fibrillation. Screening is simple and readily available, and targeted therapy improves blood pressure control and mitigates cardiovascular morbidity. Despite these imperatives, screening rates for PA are low, and mineralocorticoid-receptor antagonists are underused for hypertension treatment. After the evidence for the prevalence of PA and its associated cardiovascular morbidity is summarized, a practical approach to PA screening, referral, and management is described. All physicians who treat hypertension should routinely screen appropriate patients for PA.
Topics: Adrenal Glands; Adrenalectomy; Aldosterone; Antihypertensive Agents; Blood Pressure; Humans; Hyperaldosteronism; Hypertension; Mineralocorticoid Receptor Antagonists; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 30359120
DOI: 10.1161/CIRCULATIONAHA.118.033597 -
Journal of Internal Medicine Feb 2019Primary aldosteronism (PA), the most common form of secondary hypertension, can be either surgically cured or treated with targeted pharmacotherapy. PA is frequently... (Review)
Review
Primary aldosteronism (PA), the most common form of secondary hypertension, can be either surgically cured or treated with targeted pharmacotherapy. PA is frequently undiagnosed and untreated, leading to aldosterone-specific cardiovascular morbidity and nephrotoxicity. Thus, clinicians should perform case detection testing for PA at least once in all patients with hypertension. Confirmatory testing is indicated in most patients with positive case detection testing results. The next step is to determine whether patients with confirmed PA have a disease that can be cured with surgery or whether it should be treated medically; this step is guided by computed tomography scan of the adrenal glands and adrenal venous sampling. With appropriate surgical expertise, laparoscopic unilateral adrenalectomy is safe, efficient and curative in patients with unilateral adrenal disease. In patients who have bilateral aldosterone hypersecretion, the optimal management is a low-sodium diet and lifelong treatment with a mineralocorticoid receptor antagonist administered at a dosage to maintain a high-normal serum potassium concentration without the aid of oral potassium supplements.
Topics: Adrenalectomy; Humans; Hyperaldosteronism; Tomography, X-Ray Computed
PubMed: 30255616
DOI: 10.1111/joim.12831 -
Journal of Hypertension Oct 2020: Autonomous aldosterone overproduction represents the underlying condition of 5-10% of patients with arterial hypertension and carries a significant burden of mortality...
Genetics, prevalence, screening and confirmation of primary aldosteronism: a position statement and consensus of the Working Group on Endocrine Hypertension of The European Society of Hypertension.
: Autonomous aldosterone overproduction represents the underlying condition of 5-10% of patients with arterial hypertension and carries a significant burden of mortality and morbidity. The diagnostic algorithm for primary aldosteronism is sequentially based on hormonal tests (screening and confirmation tests), followed by lateralization studies (adrenal CT scanning and adrenal venous sampling) to distinguish between unilateral and bilateral disease. Despite the recommendations of the Endocrine Society guideline, primary aldosteronism is largely underdiagnosed and undertreated with high between-centre heterogeneity. Experts from the European Society of Hypertension have critically reviewed the available literature and prepared a consensus document constituting two articles to summarize current knowledge on the epidemiology, diagnosis, treatment, and complications of primary aldosteronism.
Topics: Aldosterone; Consensus; Humans; Hyperaldosteronism; Hypertension; Prevalence
PubMed: 32890264
DOI: 10.1097/HJH.0000000000002510 -
Endocrinology and Metabolism Clinics of... Dec 2019Primary aldosteronism used to be considered a rare cause of secondary hypertension. However, accruing evidence indicates that primary aldosteronism is more common than... (Review)
Review
Primary aldosteronism used to be considered a rare cause of secondary hypertension. However, accruing evidence indicates that primary aldosteronism is more common than previously recognized. The implications of this increased prevalence are important to public health because autonomous aldosterone production contributes to cardiovascular disease and can be treated in a targeted manner. This article focuses on clinical approaches for diagnosing primary aldosteronism more frequently and earlier in its course, as well as practical treatment objectives to reduce the risk for incident cardiovascular disease.
Topics: Humans; Hyperaldosteronism; Hypertension
PubMed: 31655770
DOI: 10.1016/j.ecl.2019.08.002